Virus Diseases Commons^™

Role Of Hiv-1 Nef Lysine Residues 4 And 7 In The Interaction With Calnexin And Inhibition Of Abca1 Activity, Valeria Kaufman, Michael Burkinsky, Md, Phd, Ruth Hunegnaw, Msc, Phd Candidate

Journal of Health Disparities Research and Practice

Patients infected with HIV are at increased risk of developing atherosclerosis, a result due partly to the functional impairment of cellular cholesterol transporter, ATP-binding cassette transporter A1 (ABCA1). This transporter mediates efflux of cholesterol from cells to high density lipoprotein, thus allowing cells to maintain normal levels of cholesterol. When ABCA1 function is inhibited, cells, and in particular macrophages, accumulate cholesterol, resulting in formation of atherosclerotic plaques. The HIV-1 protein, Nef downregulates ABCA1 and inhibits the activity of this protein, thereby reducing cholesterol efflux and promoting atherosclerosis, but the molecular mechanism by which Nef inhibits ABCA1 is unknown.

Previous studies …

Collagen Iv Assembly: Production Of A Recombinant Construct For Mechanistic Studies, Kennedy Harris, Billy Hudson, Phd, Isi Ero-Tolliver, Phd, Kyle Brown, Phd

Journal of Health Disparities Research and Practice

Basement membranes, specialized extracellular matrix, provide mechanical support for epithelial cells and shape cell behavior by interacting with cell receptors. Collagen IV, the predominant component of basement membrane, comprises six genetically distinct alpha chains (α1 to α6) that assemble to form protomers, which associate to form hexamers, in the scaffold. Non-assembly due to mutations within alpha chains give rise to kidney diseases. Yet, the mechanism of assembly is poorly understood.

Preliminary data in our lab indicated that amino acid 78 of collagen IV α2 NC1 (non-collagenous) domains may play a role in a chloride-dependent switch that supports hexamer formation. We …

Sex Differences In The Sex Differences In The Effects Of Environmental Enrichment After An Early Life Stressor, Alfredo Gutierrez, Annelyn Torres-Reverón, Phd, Raura Doreste-Méndez

Journal of Health Disparities Research and Practice

Studies have shown that environmental enrichment can compensate for the effects of an early life stressor such as maternal separation. Behavioral responses and immunohistochemical markers in rats are affected by environmental enrichment after maternal separation. In this study we seek to investigate whether sex influences the behavioral responses of environmental enrichment after maternal separation.

Prior scientific evidence suggests that there are behavioral sex differences in: 1) neural processes underlying successful or failed fear extinction (Gruene et al, 2014); (2) prenatal stress exposure and response to behavioral anxiety tests (Said et al, 2015); and (3) glutamate receptor expression in response to …

Cox2 Plays An Important Role In Maintenance Of Mammary Cancer Stem Cell Population In Human Breast Cancer Cell Lines, Mayra Garcia, Shehla Pervin, Phd, Easter Thames, Meher Parveen, Phd, Melanie Baker

Journal of Health Disparities Research and Practice

Breast cancer is a malignant growth in the adipose-rich mammary gland. Initiation and progression of breast tumors involve multiple cell types, among which mammary cancer stem cells play an important role. There are two main types of adipocytes; white adipocytes have previously been found to influence the disease while brown adipocytes, which uniquely express uncoupling protein 1 (UCP1), were recently detected in breast tumors.

We have detected Myf5, a transcription factor, which is expressed in the progenitor population of brown adipocytes, in breast cancer cell lines. We also found an association between expression of Myf5 and COX2 (or Ptgs2), which …

The Role Of Integrin-Associated Protein “Pinch” In Kidney Development, Tyrone Gamble Jr, Roy Zent, Phd, Bertha C. Elias, Phd

Journal of Health Disparities Research and Practice

PINCH (a particularly interesting new cysteine-histidine-rich protein) is a protein that binds with Integrin-linked kinase and Parvin, to form an IPP complex. This complex is formed only when integrin molecules are activated upon interaction with the basement membrane. The IPP complex then acts as a platform for other proteins to come together and regulate cell signaling to and from the extracellular matrix (ECM). This allows for various cellular activities to progress like cell adhesion, migration, proliferation, etc. There are two types of PINCH proteins, PINCH-1 and PINCH-2. Studies from our group have shown that the lack of PINCH-1 in the …

Nitric Oxide And Cyclic Gmp Signaling In Cancer Therapy, Armond Dorsey, Ferid Murad, Md, Phd, Ka Bian, Md, Phd

Journal of Health Disparities Research and Practice

The nitric oxide-3’,5’-cyclic guanosine monophosphate signaling pathway (NO-cGMP signaling pathway) is a well-known signal transduction pathway which elicits several physiological processes including: cell proliferation, vasodilation, cardiac protection, etc. In this pathway, NO binds to the ferrous heme of histidine-105 on the prosthetic heme of the β₁ subunit of soluble guanylyl cyclase, resulting in the production of cGMP. This pathway, however, is inhibited in certain cancer cells—as observed in glioma cell lines. As a result, the production of cGMP is reduced. This mechanism may facilitate uncontrolled tumor cell growth.

The cancers under research—lung carcinoma, glioma, and pancreatic carcinoma—are all highly …

Potential Cost Savings Of Not Doing Cd4 Counts In Hiv Positive People In Rhode Island With An Undetectable Viral Load, Ruth Dele-Oni, Ferdinand Schumacher, Zachary Markus, Timothy Flanigan, Md

Journal of Health Disparities Research and Practice

CD4 cells fight infections in the body. When someone contacts Human Immunodeficiency Virus (HIV), their CD4 cells are taken over by HIV which turns them into manufacturers of many copies of the virus. The Viral Load (VL) measures the amount of virus in the blood. When HIV takes over the CD4 cells, the VL increases while the number of necessary CD4 cells decreases. When patients maintain stable treatment, their CD4 counts rise, and VLs may become undetectable, indicating the virus is too little to be detected in their blood. Knowing this, is frequent CD4 counts necessary for those with undetectable …

Defining The Role For Zbp-89 In Atm-Mediated Dna Damage Response To Irradiation In The Intestine, Christine Carethers, Juanita L. Merchant, Md, Phd

Journal of Health Disparities Research and Practice

ZBP-89 (ZNF148, Zfp148) is a zinc-finger transcription factor that inhibits cellular proliferation when overexpressed in cell lines. ZBP-89 forms a protein-protein interaction with p53 and Ataxia-telangiectasia mutated (ATM). However, it is unclear how the interaction modulates the function of these two proteins in vivo.

Double strand DNA breakage induced by -irradiation induces ATM phosphoinositol kinase activity, which initiates a cascade of events culminating in cell cycle arrest, DNA repair or apoptosis. Elevated levels of ZBP-89 induce growth arrest and apoptosis in gastrointestinal cell lines. Therefore, we hypothesize that ZBP-89 facilitates cell growth arrest and activation of the DNA repair pathway …

Induction Of Dusp9 In Xenografts From Human Breast Cancer Cell Lines Increases Mammary Cancer Stem Cells, Albert Barrios, Meher Parveen, Phd, Easter Thames, Melanie Baker, Shelha Pervin, Phd

Journal of Health Disparities Research and Practice

Breast cancer remains a complex disease that kills 40,000 women every year. Initiation and progression of breast cancer is influenced by heterogeneous groups of cells, including mammary cancer stem cells (MCSCs). Progression of this dreadful disease is driven by many signaling pathways among which MAPK pathway is highly prominent. Since targeting prominent kinases in MAPK pathway has been unsuccessful to control breast cancer, it is important to examine the phosphatases that regulate the activity of these kinases.

Using xenograft model from breast cancer cell lines, our lab has found that during the initial stages of xenograft development (week 1-4, 100-200mg …

Preparing Underrepresented High School Students To Increase Diversity In The Research And Health Professions, Dolores E. Caffey-Fleming, Ms, Mph, Christopher Reid, Md, Phd

Journal of Health Disparities Research and Practice

This article introduces the work that was done through the Coordinating Center at Charles R. Drew University of Medicine and Science.

The Step Up Program, Lawrence Agodoa, Md

Journal of Health Disparities Research and Practice

The Short-Term Research Experience Program for Underrepresented Persons (STEP-UP) was established as part of the NIDDK Strategic Plan on Minority Health Disparities. This article provides an overview and introduction of this program. All of the articles that are included in this special issue reflect the work of our coordinating centers, the mentors and their staff, as well as the students.

Long-Acting Antiretroviral Nanoformulation Development And Subcellular Trafficking, Dongwei Guo

Theses & Dissertations

The introduction of nanoformulated antiretroviral therapeutic regimens is a promising alternative to standard once a day oral treatment of HIV infection. Our lab has pioneered this effort and was successful in harnessing mononuclear phagocytes (monocytes, dendritic cells and macrophages) as nanoformulated drug carriers. The approach was developed as Trojan horses for drug transport, delivery and distribution to sites of viral replication in order to facilitate microbial elimination in HIV sanctuaries. However, the remaining challenges for current antiretroviral nanoformulations include to formulate a broad range of hydrophilic short-acting drugs, and to elucidate the mechanism of sequestered nanoparticles in macrophages at the …

Synthesis And Development Of Long-Acting Abacavir Prodrug Nanoformulations, Dhirender Singh

Theses & Dissertations

Over the past decade, work from our laboratory has demonstrated the potential of targeted nanoformulated antiretroviral therapy (nanoART) to produce sustained high plasma and tissue drug concentrations for weeks following a single intramuscular (IM) administration that can suppress ongoing viral replication and mitigate dose associated viral resistance. While progress has occurred towards developing long-acting nanoformulations for protease and nonnucleoside reverse transcriptase (RT) inhibitors, development of nanoformulations of hydrophilic nucleoside RT inhibitor drugs have remained elusive. Abacavir (ABC); a hydrophilic molecule exhibited limited utilities to develop into long-acting nanoformulation platform. Furthermore, inefficient conversion of ABC to its biological active metabolites; carbovir …

Surveillance, Epidemiological, And Virological Detection Of Highly Pathogenic H5n1 Avian Influenza Viruses In Duck And Poultry From Bangladesh, Wahedul Karim Ansari, Md Safiullah Parvej, Mohamed E. El Zowalaty, Sally Jackson, Stephen A. Bustin, Adel K. Ibrahim, Md Tanvir Rahman, Han Zhang, Mohammad Ferdousur Rahman Khan, Md Mostakin Ahamd, Md. Fasiur Rahman, Marzia Rahman, Khm Nazmul H. Nazir, Sultan Ahmed, Md Liakot Hossenn, Md Abdul Kafi, Mat Yamage, Nitish C. Debnath, Graba Ahmed, Hossam Ashour, Md Masoud, Ayman Noreddin, Md B. Rahman

Pharmacy Faculty Articles and Research

Avian influenza viruses (AIVs) continue to pose a global threat. Waterfowl are the main reservoir and are responsible for the spillover of AIVs to other hosts. This study was conducted as part of routine surveillance activities in Bangladesh and it reports on the serological and molecular detection of H5N1 AIV subtype. A total of 2169 cloacal and 2191 oropharyngeal swabs as well as 1725 sera samples were collected from live birds including duck and chicken in different locations in Bangladesh between the years of 2013 and 2014. Samples were tested using virus isolation, serological tests and molecular methods of RT-PCR. …

Hepatic Fibrosis And Immune Phenotype Vary By Hcv Viremia In Hcv/Hiv Co-Infected Subjects: A Women's Interagency Hiv Study., Seema N Desai, Jennifer L Dodge, Alan L Landay, Marshall J Glesby, Patricia S. Latham, Maria C Villacres, Audrey L French, Stephen J Gange, Ruth M Greenblatt, Marion G Peters

Pathology Faculty Publications

HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear.

In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T-cell activation (HLADR+CD38+), apoptosis (Caspase-3+), and intracellular cytokines (interferon-γ, IL-2, IL-17) were assessed using multiparametric flow-cytometry. Liver fibrosis was scored by AST to platelet ratio index (APRI).

We found liver fibrosis (APRI) …

Multipurpose Tenofovir Disoproxil Fumarate Electrospun Fibers For The Prevention Of Hiv-1 And Hsv-2 Infections., Kevin Tyo

Electronic Theses and Dissertations

Sexually transmitted infections affect hundreds of millions of worldwide. Both human immunodeficiency virus (HIV-1 and -2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir …

Cellular Minichromosome Maintenance Complex Component 5 (Mcm5) Is Incorporated Into Hiv-1 Virions And Modulates Viral Replication In The Newly Infected Cells., Steven Santos, Yuri Obukhov, Sergei Nekhai, Tatiana Pushkarsky, Beda Brichacek, Michael Bukrinsky, Sergey Iordanskiy

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The post-entry events of HIV-1 infection occur within reverse transcription complexes derived from the viral cores entering the target cell. HIV-1 cores contain host proteins incorporated from virus-producing cells. In this report, we show that MCM5, a subunit of the hexameric minichromosome maintenance (MCM) DNA helicase complex, associates with Gag polyprotein and is incorporated into HIV-1 virions. The progeny virions depleted of MCM5 demonstrated reduced reverse transcription in newly infected cells, but integration and subsequent replication steps were not affected. Interestingly, increased packaging of MCM5 into the virions also led to reduced reverse transcription, but here viral replication was impaired. …

Microrna Mir-155 Is Necessary For Efficient Gammaherpesvirus Reactivation From Latency, But Not For Establishment Of Latency, Rebecca L. Crepeau, Peisheng Zhang, Edward J. Usherwood

Dartmouth Scholarship

MicroRNA-155 (miR-155) has been shown to play significant roles in the immune response, including in the formation of germinal centers (GC) and the development and maturation of T follicular helper (Tfh) cells. There is in vitro evidence to support a critical role for cellular miR-155 and viral miR-155 homologs in the establishment of gammaherpesvirus latency in B cells. We sought to determine the contribution of miR-155 to the establishment and maintenance of latency in vivousing murine gammaherpesvirus (MHV-68) infection. MHV-68-infected mice deficient in miR-155 exhibited decreases in GC B cells and Tfh cells. However, the frequencies of spleen cells …

Social Context Surrounding Hiv Diagnosis And Construction Of Masculinity: A Qualitative Study Of Stigma Experiences Of Heterosexual Hiv Positive Men In Southwest Nigeria, Titilayo A. Okoror, Catherine O. Falade, Mary O. Walker, Agaptus Anaele

Africana Studies Faculty Scholarship

Background: Though research has documented experiences of stigma and its effects on the lives of women living with HIV/AIDS, there is limited research on heterosexual positive HIV men experience of stigma in Nigeria. This study explored how social context surrounding HIV diagnosis impacts stigma experiences of heterosexual HIV positive men and their construction of masculinity in southwest Nigeria.

Methods: Using purposive sampling, 17 heterosexual HIV positive men were recruited through community based organization to participate in two hours focus group discussions or 45 min in-depth interviews that were audio-recorded. Without using the word stigma, discussions and interviews were guided by …

The Frequency Of Influenza And Bacterial Co-Infection: A Systematic Review And Meta-Analysis., Eili Y. Klein, Bradley Monteforte, Alisha Gupta, Wendi Jiang, Larissa May, Yu-Hsiang Hsieh, Andrea Freyer Dugas

Emergency Medicine Faculty Publications

AIM: Co-infecting bacterial pathogens are a major cause of morbidity and mortality in influenza. However, there remains a paucity of literature on the magnitude of co-infection in influenza patients.

METHOD: A systematic search of MeSH, Cochrane Library, Web of Science, SCOPUS, EMBASE, and PubMed was performed. Studies of humans in which all individuals had laboratory confirmed influenza, and all individuals were tested for an array of common bacterial species, met inclusion criteria.

RESULTS: Twenty-seven studies including 3,215 participants met all inclusion criteria. Common etiologies were defined from a subset of eight articles. There was high heterogeneity in the results (I(2) …